title: Hyper-activated pro-inflammatory CD16 monocytes correlate with the severity of liver injury and fibrosis in patients with chronic hepatitis B.
abstract: BACKGROUND
  Extensive mononuclear cell infiltration is strongly correlated with liver damage in patients with chronic hepatitis B virus (CHB) infection. Macrophages and infiltrating monocytes also participate in the development of liver damage and fibrosis in animal models. However, little is known regarding the immunopathogenic role of peripheral blood monocytes and intrahepatic macrophages.
  
  
  RESULTS
  The frequencies, phenotypes, and functions of peripheral blood and intrahepatic monocyte/macrophage subsets were analyzed in 110 HBeAg positive CHB patients, including 32 immune tolerant (IT) carriers and 78 immune activated (IA) patients. Liver biopsies from 20 IA patients undergoing diagnosis were collected for immunohistochemical analysis. IA patients displayed significant increases in peripheral blood monocytes and intrahepatic macrophages as well as CD16(+) subsets, which were closely associated with serum alanine aminotransferase (ALT) levels and the liver histological activity index (HAI) scores. In addition, the increased CD16(+) monocytes/macrophages expressed higher levels of the activation marker HLA-DR compared with CD16(-) monocytes/macrophages. Furthermore, peripheral blood CD16(+) monocytes preferentially released inflammatory cytokines and hold higher potency in inducing the expansion of Th17 cells. Of note, hepatic neutrophils also positively correlated with HAI scores.
  
  
  CONCLUSIONS
  These distinct properties of monocyte/macrophage subpopulations participate in fostering the inflammatory microenvironment and liver damage in CHB patients and further represent a collaborative scenario among different cell types contributing to the pathogenesis of HBV-induced liver disease.
authors.affiliation: Research Center for Biological Therapy, Beijing 302 Hospital, Beijing, China.
authors.forename: Ji-Yuan
authors.initials: JY
authors.lastname: Zhang
authors.forename: Zheng-Sheng
authors.initials: ZS
authors.lastname: Zou
authors.forename: Ang
authors.initials: A
authors.lastname: Huang
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhang
authors.forename: Jun-Liang
authors.initials: JL
authors.lastname: Fu
authors.forename: Xiang-Sheng
authors.initials: XS
authors.lastname: Xu
authors.forename: Li-Ming
authors.initials: LM
authors.lastname: Chen
authors.forename: Bao-Sen
authors.initials: BS
authors.lastname: Li
authors.forename: Fu-Sheng
authors.initials: FS
authors.lastname: Wang
mesh_terms: D000293:Adolescent; D000328:Adult; D049109:Cell Proliferation; D005260:Female; D019694:Hepatitis B, Chronic / Q000097:blood / Q000150:complications / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000276:immunology*; D008099:Liver / Q000276:immunology / Q000473:pathology*; D008103:Liver Cirrhosis / Q000097:blood / Q000150:complications / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology; D017452:Receptors, IgG / Q000378:metabolism*; D012720:Severity of Illness Index; D058504:Th17 Cells / Q000166:cytology / Q000276:immunology; D055815:Young Adult
chemical_list: D017452:Receptors, IgG